As a conventional art, for example, Japanese Patent No. 3116311 discloses a microspherical sustained-release preparation comprised of a water-soluble drug such as a physiologically active peptide and a polylactic acid, and as a method for producing the same, there is described a method which comprises dissolving a water-soluble drug such as a physiologically active peptide and a biodegradable polymer in a mixed solvent of a water-immiscible solvent such as dichloromethane and a water-miscible solvent such as ethanol, and adding the solution into water etc. to produce an O/W emulsion, followed by subjecting to an in-water drying method to prepare a sustained-release microcapsule. In addition, Japanese Patent No. 3512408 discloses microspherical microparticles comprising of a water-soluble physiologically active peptide and a polylactic acid or a copolymer of lactic acid and glycolic acid, wherein the release dynamic of the drug is controlled, and as a method for preparing the microparticle, there is described a method which comprises dissolving a polymer in a volatile and water-immiscible solvent, mixing a solution separately prepared by dissolving a water-soluble physiologically active peptide in water-miscible solvent with the above polymer solution, and emulsifying the resulting solution in an aqueous phase containing an emulsifier, followed by removing the solvent from the obtained O/W emulsion to prepare the microspherical microparticles. However, the drug content in each of the sustained-release preparations is about 10% or about 0.1 to 5%, and a sustained-release preparation capable of sustainably releasing the drug over about two months is not described.
Furthermore, Pharmaceutical Research, Vol. 19, No. 4 (April, 2002) discloses a microspherical sustained-release preparation comprised of leuprolide acetate and polylactic acid, and as a process for preparing the preparation, there is described a method which comprises mixing a methanol solution of leuprolide and a dichloromethane solution of polylactic acid, and dispersing the solution in an aqueous solution of polyvinylalcohol, followed by removing the organic solvent to prepare the microspherical sustained-release preparation. The preparation has a characteristic of releasing the drug over a period of 180 to 240 days. However, the drug release is small in amount at the first or second month from the early period of administration after initial burst, and the preparation exhibits a typical triphasic drug release.